2-Chloro-N-(4′-chlorobiphenyl-2-yl)-nicotinamide, having the common name boscalid, is a compound with the structural formula I:

Boscalid is a fungicide of the carboxamide group and acts as a succinate dehydrogenase inhibitor (SDHI), a respiratory inhibitor of mitochondria. It was first registered for commercial use in 2003 and is now registered in over 50 countries including Europe and America.
EP 0545099 discloses nicotinamides, anilide derivatives and 2-aminobiphenyl derivatives and their use for controlling Botrytis. The subject compounds are defined by way of a Markush formula.
U.S. Pat. No. 7,241,896 concerns a process for producing 2-halogen-pyridine-carboxylic acid amides. The preparation of boscalid is disclosed and exemplified. Boscalid is synthesized by the reaction of 2-chloro-3-nicotinyl chloride II with 2-(4-chlorophenyl)aniline in a solvent system. Boscalid was crystallized by cooling an organic solution, after extraction with sodium carbonate solution. Examples of water-immiscible organic solvents indicated in U.S. Pat. No. 7,241,896 include aromatic, aliphatic and cycloaliphatic hydrocarbons, aromatic, aliphatic and cycloaliphatic halogenated hydrocarbons, acyclic ethers, preferably having from 4 to 10 carbon atoms, esters having from 3 to 10 carbon atoms, preferably those of aliphatic or cycloaliphatic alcohols preferably with aliphatic carboxylic acids, for example esters of acetic acid, propionic acid or butyric acid with C3 C8 alkanols, such as methyl, ethyl, n-propyl, n-butyl or isobutyl acetate, propionate, butyrate, and the like, ketones, preferably having from 4 to 10 carbon atoms, such as methyl ethyl ketone, and also aliphatic nitriles preferably having from 4 to 10 carbon atoms, such as butyronitrile, as well as mixtures of the aforementioned organic solvents. Xylene appears to be the preferred solvent of U.S. Pat. No. 7,241,896.
U.S. Pat. No. 8,350,046 discloses a process for preparing arylcarboxamides by reacting an acid chloride with an arylamine in a non-aqueous solvent. Toluene appears to be the preferred solvent of U.S. Pat. No. 8,350,046.
U.S. Pat. No. 7,087,239 concerns crystalline hydrates of nicotinic acid anilide and benzoyl anilide derivatives. The synthesis and recovery of the hydrate of boscalid is specifically exemplified in U.S. Pat. No. 7,087,239. The hydrate is obtained by first preparing the anhydrate of boscalid, which is obtained at the end of the synthesis procedure as a solution in hot xylene. Upon cooling, boscalid crystallized from the solution and was dried under vacuum in an oven. The anhydrate is indicated to have the following physical properties:
Molecular weight [g/mol]:343.2Melting point [° C.] (DSC):145.2Density [g/mol]:1.42X-ray reflection (2θ degree):18; 22.5; 9.5; 6Cu-KαIR absorption [cm−1]:1650Water content [%]:<1
U.S. Pat. No. 7,087,239 discloses that the hydrate can be formed by dissolving the anhydrate in tetrahydrofuran (THF) at 40° C. and the resulting solution added to water. The precipitate was removed by filtration and dried, to yield the monohydrate of boscalid. The crystalline modification of the anhydrate of boscalid disclosed in U.S. Pat. No. 7,087,239 is referred to herein as the polymorph I of the anhydrate of boscalid.
U.S. Pat. No. 7,501,384 discloses an allegedly novel crystalline modification of the anhydrate of boscalid. The crystalline modification disclosed in U.S. Pat. No. 7,501,384 is referred to herein as the polymorph II of the anhydrate of boscalid. It is suggested in U.S. Pat. No. 7,501,384 that the polymorph II of the anhydrate of boscalid is more suitable for making formulations which require grinding/milling processes.
U.S. Pat. No. 7,501,384 describes that the polymorph II of the anhydrate of boscalid may be prepared by a process comprising:
a) dissolving the polymorph I of the anhydrate of boscalid in a polar organic solvent or an aromatic hydrocarbon; and
b) precipitation of the polymorph II of the anhydrate of boscalid by cooling the solvent.
An alternative process for the preparation of the polymorph II of the anhydrate of boscalid disclosed in U.S. Pat. No. 7,501,384 comprises:
a) heating the polymorph I of the anhydrate of boscalid to above 150° C. until melted; and
b) cooling the melt with the addition of seed crystals of the polymorph II of the anhydrate of boscalid.
U.S. Pat. No. 7,501,384 describes the polymorph II of the anhydrate of boscalid as having the following properties:
Molecular weight [g/mol]:342Melting point [° C.] (DSC):147.2Heat of fusion [J/g] (DSC):106Density [g/cm3]:1.457Characteristic IR bands [cm−1]:868, 917, 1675
The cell parameters from the crystallographic investigations of the polymorph II of the anhydrate of boscalid using a single crystal diffractometer from Siemens are given in U.S. Pat. No. 7,501,384 as follows:
Class:MonoclinicSpace group:P21/ca:1162.5(6) pmb:1134.2(4) pmc:1283.2(5) pmα:90°β:114.52(4)°γ:90°Volume:1.5390 nm−3Z:4Density 1.481 mg/m−3(calculated):R1, wR2:0.0489; 0.1264
The parameters indicated above have the following meanings:
a, b, c=edge lengths of the unit cell;
α, β, γ=corresponding angles; and
Z=number of molecules in the unit cell.
FTIR spectrometry may be used to record IR spectra.